Although public attention has focused largely on Lyme disease, an array of spirochetal, protozoan, viral and rickettsial pathogens concurrently infect residents of sites in the eastern US in which deer are abundant. The abundance of deer and that of the vector arthropods that depend on this host recently have increased. Our objective, therefore, is to describe the frequency of human coinfection associated with the presence of deer in this region and to determine whether the resulting spectrum of disease may reflect a synergy between pathogens. In particular, we shall: (1) Determine how frequently deer-associated pathogens infect residents of the northeastern US and how frequently these pathogens occur in combination. Although we shall focus on the agents of Lyme disease, babesiosis, human granulocytic ehrlichiosis and TBE-group arboviruses, we shall seek to document the presence of other tick-borne microbes and the frequency of infection by such deer-associated, mosquito- transmitted agents as Jamestown Canyon virus and Cache Valley fever virus. We shall determine prospectively how frequently deer-associated pathogens infect residents of our study sites by means of a seroprevalence study and how frequently they cause disease by means of a case-finding study. (2) Estimate the burden on human health imposed by these deer-associated pathogens and determine whether coinfection synergizes pathogenesis. In particular, we shall determine whether coinfected people experience a greater diversity of symptoms or duration of illness than the sum of symptoms due to each pathogen. The severity of apparent deer-associated disease will be compared in a previously described population of patients with Lyme disease alone, babesiosis alone and Lyme disease and babesiosis coinfection. A cohort of patients expressing symptoms of deer-associated infection will be enrolled in a prospective longitudinal study. We shall compare the clinical outcome of patients with a single infection alone to that of coinfected patients. (3) Determine how frequently people become exposed to these deer-associated pathogens by deriving a series of entomological inoculation rates which synthesize estimates of vector density and prevalence of infection by particular pathogens. In each study site, we shall describe the prevalence of deer-associated pathogens in their vector populations and the density of these vectors relative to people. The density of deer will be estimated in each site. This proposed effort will help define the health burden imposed on people residing in proximity to deer and will contribute to diagnosis and case-management of apparent Lyme disease.